Evaluation of the osteoinductive potential of a bio-inspired scaffold mimicking the osteogenic niche for bone augmentation

Abstract

Augmentation of regenerative osteogenesis represents a premier clinical need, as hundreds of thousands of patients are left with insufficient healing of bony defects related to a host of insults ranging from congenital abnormalities to traumatic injury to surgically-induced deficits. A synthetic material that closely mimics the composition and structure of the human osteogenic niche represents great potential to successfully address this high demand. In this study, a magnesium-doped hydroxyapatite/type I collagen scaffold was fabricated through a biologically-inspired mineralization process and designed to mimic human trabecular bone. The composition of the scaffold was fully characterized by XRD, FTIR, ICP and TGA, and compared to human bone. Also, the scaffold microstructure was evaluated by SEM, while its nano-structure and nano-mechanical properties were evaluated by AFM. Human bone marrow-derived mesenchymal stem cells were used to test the in vitro capability of the scaffold to promote osteogenic differentiation. The cell/scaffold constructs were cultured up to 7 days and the adhesion, organization and proliferation of the cells were evaluated. The ability of the scaffold to induce osteogenic differentiation of the cells was assessed over 3 weeks and the correlate gene expression for classic genes of osteogenesis was assessed. Finally, when tested in an ectopic model in rabbit, the scaffold produced a large volume of trabecular bone in only two weeks, that subsequently underwent maturation over time as expected, with increased mature cortical bone formation, supporting its ability to promote bone regeneration in clinically-relevant scenarios. Altogether, these results confirm a high level of structural mimicry by the scaffold to the composition and structure of human osteogenic niche that translated to faster and more efficient osteoinduction in vivo--features that suggest such a biomaterial may have great utility in future clinical applications where bone regeneration is required.

Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

“…49,50 Hence, we provided a new method for biomimetic mineralization based on the PILP strategy, in which collagen gels after self-assembly, but not dry collagen scaffolds, were immersed into the CMC/ ACP nanocomplex solution. Compared with the direct mixing of collagen solution and mineral ions 11,46,47 or immersing the dry collagen scaffolds in the mineral solution, 13,23,51 the mineralized method described in this study can cause the collagen scaffold to have a water oversaturated status after self-assembly. This status may make the nanocomplexes of CMC/ACP more easily intercalate into the interstices of the collagen fibrils, which is the crux of intrafibrillar mineralization of collagen scaffolds.…”

“…[1][2][3][4][5][6][7] Among these biomaterials, type 1 9 To date, mixing collagen with minerals and mineralizing collagen have been used to modify collagen scaffolds for simulating the composition and microstructure of bone tissue to the greatest extent possible. [10][11][12][13][14][15][16][17] Because HA is a primary mineral component of natural bone and possesses outstanding bioactivity, osteoconductivity, biocompatibility with bone cells, good mechanical properties, and a slow degradation rate in vivo, it has often been the first choice for modifying collagen scaffolds. 10,[18][19][20] Although directly mixing collagen with HA powders in certain proportions can result in collagen scaffolds with compositions similar to those of natural bone tissues, it is difficult to simulate their microstructure and microenvironment via this process.…”

“…This result may be due to the significant effect of mineral HA of osteoblastic differentiation of preosteoblasts (3T3-E1) in vitro. 11,61 The ALP activity on the TMC scaffolds was slightly higher than that on the BMC scaffolds at the beginning of the test (Figure 10). This may be due to the earlier contacts between 3T3-E1 and HA on the TMC scaffolds while the cells were still proliferating on the BMC scaffolds.…”

Evaluation of zinc-doped mesoporous hydroxyapatite microspheres for the construction of a novel biomimetic scaffold optimized for bone augmentation

“…It was reported that the magnesium-doped hydroxyapatite/ collagen scaffold mimicking the hypoxic condition in the osteogenic niche might be responsible for maintaining the cells in a quiescent state. 9,39 On the other hand, ion-induced cell death such as that from excessive Ca 2+ may account for lower cell viability resulting from the initial ion release from the composite scaffolds. 40,41 Collagen-based materials that serve as analogs of organic components of bone matrix have previously been developed for bone regeneration.…”

“…6,7 The hydroxyapatite/collagen composite scaffolds mimicking the structure and composition of trabecular bone were extensively investigated, and they have been shown to have great potential in bone repair and regeneration. [8][9][10] The hydroxyapatite-collagen pairing naturally occurs in bone, whereby the collagen matrix provides strength and structural stability, whereas hydroxyapatite reinforces the organic matrix. 11 The organic matrix containing collagen and noncollagenous proteins plays an important role in mineralization, during which the organic matrix not only directs mineral deposition but also guides its growth.…”